Genomic characterization of Achromobacter species isolates from chronic and occasional lung infection in cystic fibrosis patients

Abstract

Achromobacter species are increasingly being detected in cystic fibrosis (CF) patients, where they can establish chronic infections by adapting to the lower airway environment. To better understand the mechanisms contributing to a successful colonization by Achromobacter species, we sequenced the whole genome of 54 isolates from 26 patients with occasional and early/late chronic lung infection. We performed a phylogenetic analysis and compared virulence and resistance genes, genetic variants and mutations, and hypermutability mechanisms between chronic and occasional isolates. We identified five Achromobacter species as well as two non-affiliated genogroups (NGs). Among them were the frequently isolated Achromobacter xylosoxidans and four other species whose clinical importance is not yet clear: Achromobacter insuavis, Achromobacter dolens, Achromobacter insolitus and Achromobacter aegrifaciens . While A. insuavis and A. dolens were isolated only from chronically infected patients and A. aegrifaciens only from occasionally infected patients, the other species were found in both groups. Most of the occasional isolates lacked functional genes involved in invasiveness, chemotaxis, type 3 secretion system and anaerobic growth, whereas the great majority (>60%) of chronic isolates had these genomic features. Interestingly, almost all (n=22/23) late chronic isolates lacked functional genes involved in lipopolysaccharide production. Regarding antibiotic resistance, we observed a species-specific distribution of blaOXA genes, confirming what has been reported in the literature and additionally identifying blaOXA-2 in some A. insolitus isolates and observing no blaOXA genes in A. aegrifaciens or NGs. No significant difference in resistance genes was found between chronic and occasional isolates. The results of the mutator genes analysis showed that no occasional isolate had hypermutator characteristics, while 60% of early chronic (<1 year from first colonization) and 78% of late chronic (>1 year from first colonization) isolates were classified as hypermutators. Although all A. dolens, A. insuavis and NG isolates presented two different mutS genes, these seem to have a complementary rather than compensatory function. In conclusion, our results show that Achromobacter species can exhibit different adaptive mechanisms and some of these mechanisms might be more useful than others in establishing a chronic infection in CF patients, highlighting their importance for the clinical setting and the need for further studies on the less clinically characterized Achromobacter species.

An 18-Year Dataset on the Clinical Incidence and MICs to Antibiotics of Achromobacter spp. (Labeled Biochemically or by MAL-DI-TOF MS as A. xylosoxidans), Largely in Patient Groups Other than Those with CF

“…xylosoxidans is more and more frequently referred to as an important emerging pathogen. Although most of the attention in the literature in this context has been focused on patients with cystic fibrosis [1][2][3]10,13,15,[17][18][19], the microorganism has also been shown to pose an increasingly important threat to numerous other patient groups, among which-most importantly-are those with underlying oncological malignancies [7][8][9]11,14,20] and those in intensive care units [12,16,21]. Our data do not corroborate this notion, but our study cannot be compared to the majority of studies in the literature, given that cystic fibrosis patients-the most important patient group in this context-are underrepresented in our study.…”

“…The overall amount of clinical samples likewise increased by 50% from 2012 to 2013, and another 35% from 2013 to 2020. Nevertheless, selection pressure from antibiotic therapy and the longer survival of cystic fibrosis patients [15], oncological and immunosuppressed patients could also have contributed a certain amount.…”

“…Antibiotics 2021, 10, x FOR PEER REVIEW 2 of 14 selection pressure from antibiotic therapy and the longer survival of cystic fibrosis patients [15]. All of the evidence highlights a growing need for clinical data, as well as in depth analyses on the potential pathogenicity and antibiotic resistance profile of this emerging pathogen [1,15,16].…”

“…isolates from respiratory samples of cystic fibrosis patients have been reported as increasing in recent years, which has been attributed to selection pressure from antibiotic therapy and the longer survival of cystic fibrosis patients [15]. All of the evidence highlights a growing need for clinical data, as well as in depth analyses on the potential pathogenicity and antibiotic resistance profile of this emerging pathogen [1,15,16]. We Antibiotics 2022, 11, 311 2 of 14 contribute to the matter by providing a 444-isolate dataset (314 clinical and 130 screening isolates) in which Achromobacter spp.…”

Achromobacter spp. Adaptation in Cystic Fibrosis Infection and Candidate Biomarkers of Antimicrobial Resistance

“…In particular, chronic colonization has been associated with a decline in respiratory function, increased frequency of exacerbations and lung inflammation [ 1 ]. Although virulence factors supporting invasiveness and survival have been described (e.g., swimming motility, biofilm formation, lipopolysaccharide, type III secretion system, phospholipase C, proteases) [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ], virulence features related to the ability of Achromobacter spp. to colonize the lungs of CF patients chronically or occasionally are still not fully clear.…”